We hypothesize that specific vascular addresses within tumor vasculature can be exploited for imaging and detection of metastatic breast carcinoma; our goal is to use these biochemical differences to develop targeted therapies. Here, we propose to investigate the molecular diversity of angiogenic vasculature during the tumor progression and metastases of breast cancer. Our specific aims are (i) to identify and characterize suitable markers of bone marrow metastases as targets for vascular imaging; (ii) to study the localization and distribution of the probes and respective receptors by imaging systems; (iii) to design, synthesize and validate devices for targeted imaging by developing novel tools for intravital imaging at the protein-protein level (such as engineered phage particles, recombinant proteins, nanoshells, or fluorescent microspheres). The most efficient targeting systems will be tested and validated in vivo in mouse models of bone marrow metastases. If successful, novel strategies to image metastatic breast cancer will be derived from this application. The approaches utilized in this application can be used to characterize the tumor microenvironment in breast cancer, changes and localization of receptors in the vascular endothelium of tumor blood vessels during breast cancer progression. In addition, probes that target breast cancer vasculature will be developed as delivery tools and will likely enhance effectiveness of current imaging technology.